Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics

Handle URI:
http://hdl.handle.net/10754/558766
Title:
Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics
Authors:
Roy, S.; Schmeier, S.; Arner, E.; Alam, Tanvir ( 0000-0003-4844-0171 ) ; Parihar, S. P.; Ozturk, M.; Tamgue, O.; Kawaji, H.; de Hoon, M. J. L.; Itoh, M.; Lassmann, T.; Carninci, P.; Hayashizaki, Y.; Forrest, A. R. R.; Bajic, Vladimir B. ( 0000-0001-5435-4750 ) ; Guler, R.; Consortium, F.; Brombacher, F.; Suzuki, H.
Abstract:
Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff, (M1) and Hivep1, Nfil3, Prdm1, (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics 2015 Nucleic Acids Research
Journal:
Nucleic Acids Research
Issue Date:
27-Jun-2015
DOI:
10.1093/nar/gkv646
Type:
Article
ISSN:
0305-1048; 1362-4962
Additional Links:
http://nar.oxfordjournals.org/lookup/doi/10.1093/nar/gkv646
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorRoy, S.en
dc.contributor.authorSchmeier, S.en
dc.contributor.authorArner, E.en
dc.contributor.authorAlam, Tanviren
dc.contributor.authorParihar, S. P.en
dc.contributor.authorOzturk, M.en
dc.contributor.authorTamgue, O.en
dc.contributor.authorKawaji, H.en
dc.contributor.authorde Hoon, M. J. L.en
dc.contributor.authorItoh, M.en
dc.contributor.authorLassmann, T.en
dc.contributor.authorCarninci, P.en
dc.contributor.authorHayashizaki, Y.en
dc.contributor.authorForrest, A. R. R.en
dc.contributor.authorBajic, Vladimir B.en
dc.contributor.authorGuler, R.en
dc.contributor.authorConsortium, F.en
dc.contributor.authorBrombacher, F.en
dc.contributor.authorSuzuki, H.en
dc.date.accessioned2015-07-02T07:52:27Zen
dc.date.available2015-07-02T07:52:27Zen
dc.date.issued2015-06-27en
dc.identifier.citationRedefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics 2015 Nucleic Acids Researchen
dc.identifier.issn0305-1048en
dc.identifier.issn1362-4962en
dc.identifier.doi10.1093/nar/gkv646en
dc.identifier.urihttp://hdl.handle.net/10754/558766en
dc.description.abstractClassically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff, (M1) and Hivep1, Nfil3, Prdm1, (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.en
dc.relation.urlhttp://nar.oxfordjournals.org/lookup/doi/10.1093/nar/gkv646en
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.titleRedefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomicsen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalNucleic Acids Researchen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDivision of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japanen
dc.contributor.institutionRiken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japanen
dc.contributor.institutionMassey University, Institute of Natural and Mathematical Sciences, Auckland, New Zealanden
dc.contributor.institutionInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, South Africaen
dc.contributor.institutionUniversity of Cape Town, Health Science Faculty, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, Cape Town, South Africaen
dc.contributor.institutionRiken Preventive Medicine and Diagnosis Innovation Program (PMI), 1–7–22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japanen
kaust.authorAlam, Tanviren
kaust.authorBajic, Vladimir B.en
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